Airway remodeling in asthma: what really matters

Abstract

Airway remodeling is generally quite broadly defined as any change in composition, distribution, thickness, mass or volume and/or number of structural components observed in the airway wall of patients relative to healthy individuals. However, two types of airway remodeling should be distinguished more clearly: (1) physiological airway remodeling, which encompasses structural changes that occur regularly during normal lung development and growth leading to a normal mature airway wall or as an acute and transient response to injury and/or inflammation, which ultimately results in restoration of a normal airway structures; and (2) pathological airway remodeling, which comprises those structural alterations that occur as a result of either disturbed lung development or as a response to chronic injury and/or inflammation leading to persistently altered airway wall structures and function. This review will address a few major aspects: (1) what are reliable quantitative approaches to assess airway remodeling? (2) Are there any indications supporting the notion that airway remodeling can occur as a primary event, i.e., before any inflammatory process was initiated? (3) What is known about airway remodeling being a secondary event to inflammation? And (4), what can we learn from the different animal models ranging from invertebrate to primate models in the study of airway remodeling? Future studies are required addressing particularly pheno-/endotype-specific aspects of airway remodeling using both endotype-specific animal models and "endotyped" human asthmatics. Hopefully, novel in vivo imaging techniques will be further advanced to allow monitoring development, growth and inflammation of the airways already at a very early stage in life.

Keywords: Airway pathology; Airway remodeling; Asthma.

Fig. 1

Fraction of epithelial basal membrane (BM) of human endobronchial biopsies exhibiting complete denudation is inversely correlated with biopsy volume (=size), which was estimated according to the Cavalieri Principle. Figure by courtesy of Dr. V.A. Bratu, modified from Bratu (2008); Fig. 3.4c

Fig. 2

Intra-epithelial eosinophilic granulocyte (arrowhead) in main bronchus of a murine lung chronically challenged with ovalbumin according to the protocol of Wegmann et al. (2005). Tissue was fixed with 4% paraformaldehyde, embedded into glycol methacrylate and the section was Congo Red-stained for eosinophils. AE airway epithelium. Black arrows indicate eosinophilic granulocytes in subepithelial interstitial tissue

Fig. 3

Transmission electron micrograph of a cross-section through a terminal airway branch derived from the respiratory tract of Drosophila melanogaster, 3rd instar larva. Tissue was processed as described elsewhere (Fehrenbach et al. 1987). Ultrathin sections were cut on an Ultracut E microtome, collected on formvar-coated nickel grids, stained with lead citrate and analyzed using a Zeiss EM 900. AS airway space; BL basal lamina; Cu cuticula; Ep epithelium; Nu nucleus and MC muscle cells. Black arrowheads indicate a cellular junction